DESC:FIELD
The present disclosure relates to a novel crystalline form of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
BACKGROUND
5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole (Ethiprole) is one of the important fluorine bearing 1-aryl pyrazole derivatives developed in the recent past. Ethiprole has the following structure:

Ethiprole is a non-systemic, broad-spectrum phenyl-pyrazole insecticide that is effective at low application rates against plant hoppers, thrips, aphids, weevils, flies, maggots, grasshoppers, psyllids, leaf miners and some species of whitefly. Good activity against stink bugs in rice has also been reported.
The mode of action of Ethiprole is different from many other insecticides including pyrethroids, organophosphates, chloronicotinyls and carbamates and there is little potential for cross-resistance with those classes. Consequently, Ethiprole has good potential for use in the insect-resistance management programs where it can be used with other insecticides in alternate spray programs, tank-mix combinations or premixes.
A repellent effect against certain insects has been noted for Ethiprole. The effect has been observed with termites, cockroaches, rice bugs and wireworms. The selective toxicity is due to the higher potency of Ethiprole in the insect than in vertebrates.
It is known that, Ethiprole alone or in combination with other insecticides has shown to provide good pest control over the trial period of 6 months, regardless of the storage temperature.
Various processes for the synthesis of Ethiprole are disclosed in the patent documents WO9722593, US6410737 and CN101168529. These patent documents disclose the method of synthesis of sulfinyl precursor of Ethiprole and its subsequent oxidation to obtain Ethiprole.
The environmental and economic requirements imposed by the government on the modern-day fungicides and insecticides are continually increasing, with regard to the spectrum of action, toxicity, selectivity, application rate, formation of residues and favorable preparation ability. There is also the problem of development of resistance in insecticides to known active compounds.
It is therefore, a constant task to develop new fungicide and insecticide agents which in some areas have advantages over their known counterparts.
OBJECTS
Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:
An object of the present disclosure is to provide a novel crystalline form of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
Another object of the present disclosure is to provide a process for the preparation of the crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
Other objects and advantages of the present disclosure will be more apparent from the following description, which is not intended to limit the scope of the present disclosure.

SUMMARY
The present invention relates to a novel crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole. The crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole is further described using X-ray powder diffraction patterns. X-ray powder diffraction pattern of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole is characterized by the presence of peaks expressed as 2? at about 13.45 ± 0.2, 13.71 ± 0.2, 14 94 ± 0.2, 16.67 ± 0.2, 20.53 ± 0.2, 20.79 ± 0.2, 21.46 ± 0.2, 22.38± 0.2, 22.65 ± 0.2, 23.15 ± 0.2, 23.79 ± 0.2, 24.54 ± 0.2, 26.20 ± 0.2, 28.27 ± 0.2, 29.55 ± 0.2, 30.05 ± 0.2, 30.36 ± 0.2, 32.89 ± 0.2, 34.70 ± 0.2, 36.25 ± 0.2 and 36.66 ± 0.2 degrees.
Further, the crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole is characterized by an infrared spectrum comprising peaks at wavenumbers of 1008 cm-1, 1317 cm-1 and 2247 cm-1.
The crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole is characterized by differential scanning calorimetry (DSC).
Furthermore, the present invention provides a process for the preparation of the crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an X-ray powder diffraction spectrum of crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using ethanol as a fluid medium.
Figure 2 is an X-ray powder diffraction spectrum of crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using methanol as a fluid medium.
Figure 3 is an IR spectrum of crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using ethanol as a fluid medium.
Figure 4 is an IR spectrum of crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using methanol as a fluid medium.
Figure 5 is differential scanning calorimetry (DSC) of crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using ethanol as a fluid medium.
Figure 6 is DSC of crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using methanol as a fluid medium.
DETAILED DESCRIPTION
Ethiprole is an insecticide that is effective at low application rates against plant hoppers, thrips, aphids, weevils, flies, maggots, grasshoppers, psyllids, leaf miners and some species of whitefly.
It is known that, Ethiprole alone or in combination with other insecticides has shown to provide good pest control over the trial period of 6 months, regardless of the storage temperature. Ethiprole has the following structure:

The present invention provides a novel crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole. The present invention also provides a process of preparation of the crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
In accordance with one aspect of the present invention, there is provided a novel crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
X-ray powder diffraction pattern of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole having peaks expressed as 2? at about 13.45 ± 0.2, 13.71 ± 0.2, 14 94 ± 0.2, 16.67 ± 0.2, 20.53 ± 0.2, 20.79 ± 0.2, 21.46 ± 0.2, 22.38± 0.2, 22.65 ± 0.2, 23.15 ± 0.2, 23.79 ± 0.2, 24.54 ± 0.2, 26.20 ± 0.2, 28.27 ± 0.2, 29.55 ± 0.2, 30.05 ± 0.2, 30.36 ± 0.2, 32.89 ± 0.2, 34.70 ± 0.2, 36.25 ± 0.2 and 36.66 ± 0.2 degrees.
The crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using ethanol as a fluid medium is characterized by an X-ray powder diffraction pattern having peaks as listed in Table 1.
Table 1: Characteristic peaks and interplanar distances of the novel crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using ethanol as a fluid medium
Peak No 2? Degrees d (A?)
1 13.48 6.5632
2 13.70 6.4583
3 14.96 5.9170
4 16.69 5.3074
5 20.57 4.3142
6 20.79 4.2691
7 21.47 4.1354
8 22.39 3.9675
9 22.65 3.9225
10 23.18 3.8340
11 23.81 3.7340
12 24.55 3.6231
13 26.24 3.3934
14 28.28 3.1531
15 29.58 3.0174
16 30.04 2.9723
17 30.37 2.9407
18 32.88 2.7217
19 34.73 2.5809
20 36.27 2.4747
21 36.63 2.4512

A crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole using ethanol as a fluid medium is characterized by an X-ray powder diffraction pattern as in Figure 1.
The crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using methanol as a fluid medium is characterized by an X-ray powder diffraction pattern having peaks as listed in Table 2.
Table 2: Characteristic peaks and interplanar distances of the novel crystalline form of 5-amino-1-(2, 6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole prepared using methanol as a fluid medium
Peak No 2? Degrees d (A?)
1 13.41 6.5973
2 13.72 6.4489
3 14.92 5.9328
4 16.65 5.3201
5 20.49 4.3309
6 20.79 4.2691
7 21.44 4.1411
8 22.36 3.9727
9 22.65 3.9225
10 23.12 3.8438
11 23.77 3.7402
12 24.52 3.6274
13 26.16 3.4036
14 28.25 3.1564
15 29.51 3.0244
16 30.05 2.9713
17 30.35 2.9426
18 32.89 2.7209
19 34.66 2.5859
20 36.23 2.4774
21 36.69 2.4474

A crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole using methanol as a fluid medium is characterized by an X-ray powder diffraction pattern as in Figure 2.
In accordance with one embodiment of the present disclosure, the crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole exhibit an X-ray powder diffractogram at 25 °C.
In accordance with another aspect of the present disclosure, there is provided a process for the preparation of the crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole, the process comprises the following steps:
In the first step, a predetermined amount of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole and a predetermined amount of a hydrocarbon solvent are mixed to obtain a slurry.
In the second step, the slurry is heated to a reflux temperature of the hydrocarbon solvent for a predetermined time period to obtain a heated slurry.
In the third step, the heated slurry is cooled to a first predetermined temperature to obtain the mixture.
In the fourth step, the mixture is filtered to obtain solid; and
In the fifth step, the solid is washed with the hydrocarbon solvent and dried at a second predetermined temperature to obtain the crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole.
In accordance with the present disclosure, the hydrocarbon solvent is at least one selected from the group consisting of methanol and ethanol.
In accordance with one embodiment of the present disclosure, the hydrocarbon solvent is methanol.
In accordance with another embodiment of the present disclosure, the hydrocarbon solvent is ethanol.
In accordance with the present disclosure, the predetermined time period ranges from 15 to 120 minutes.
In accordance with the present disclosure, the first predetermined temperature ranges from 20 to 80 °C.
In accordance with the present disclosure, the second predetermined temperature ranges from 40 to 80 °C.
In accordance with one embodiment of the present disclosure, the second predetermined temperature is 60 °C.
The present disclosure is further illustrated herein below with the help of the following examples. The experiments used herein are intended merely to facilitate an understanding of the ways in which the embodiments herein may be practiced and to further enable those of skilled in the art to practice the embodiments herein. Accordingly, the experiments should not be construed as limiting the scope of the embodiments herein.
Example 1:
A reactor was charged with 228 mL of ethanol. 57 g of Ethiprole was introduced in ethanol to obtain a mixture. The Mixture was heated to reflux and maintained for 1 hour to obtain a slurry. The slurry was cooled to 75 °C. The cooled slurry was filtered to obtain a solid. The solid was washed with ethanol and dried at 60 °C to obtain the crystalline form of Ethiprole.
The crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole or ethiprole prepared using ethanol as a fluid medium is characterized by:
• an X-ray powder diffraction pattern as depicted in Figure 1;
• an IR spectrum as depicted in Figure 3; and
• Differential scanning calorimetry (DSC) as depicted in Figure 5.
Example 2:
A reactor was charged with75 mL of methanol. 25 g of Ethiprole was introduced in methanol to obtain a mixture. The Mixture was heated at 65 °C for 30 minutes to obtain a slurry. The slurry was cooled to 28 °C. The cooled slurry was filtered to obtain a solid. The solid was washed with methanol and dried at 60 °C to obtain the crystalline form of Ethiprole.
A crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole or ethiprole prepared using methanol as a fluid medium is characterized by:
• an X-ray powder diffraction pattern as depicted in Figure 2;
• an IR spectrum as depicted in Figure 4; and
• Differential scanning calorimetry as depicted in Figure 6.
TECHNICAL ADVANCEMENT
• A novel crystalline form of Ethiprole is provided.
• A process of preparation of the crystalline form of Ethiprole is simple and economic.
Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the invention to achieve one or more of the desired objects or results. While certain embodiments of the inventions have been described, these embodiments have been presented by way of experiment only, and are not intended to limit the scope of the inventions. Variations or modifications to the composition of this invention, within the scope of the invention, may occur to those skilled in the art upon reviewing the disclosure herein. Such variations or modifications are well within the spirit of this invention.
The numerical values given for various physical parameters, dimensions and quantities are only approximate values and it is envisaged that the values higher than the numerical value assigned to the physical parameters, dimensions and quantities fall within the scope of the invention unless there is a statement in the specification to the contrary.
While considerable emphasis has been placed herein on the specific features of the preferred embodiment, it will be appreciated that many additional features can be added and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other changes in the preferred embodiment of the disclosure will be apparent to those skilled in the art from the disclosure herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the disclosure and not as a limitation. ,CLAIMS:1. A crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole, characterized by an X-ray powder diffraction pattern having peaks expressed as 2? at about 13.45 ± 0.2, 13.71 ± 0.2, 20.79 ± 0.2, 21.46 ± 0.2, 22.38± 0.2, 23.15 ± 0.2, 23.79 ± 0.2, 26.20 ± 0.2, 28.27 ± 0.2, 34.70 ± 0.2 and 36.25 ± 0.2 degrees.
2. The crystalline form as claimed in claim 1, which further includes peaks expressed as 2? at about 14. 94 ± 0.2, 16.67 ± 0.2, 20.53 ± 0.2, 22.65 ± 0.2, 24.54 ± 0.2, 29.55 ± 0.2, 30.05 ± 0.2, 30. 36 ± 0.2 32.89 ± 0.2, and 36.66 ± 0.2 degrees.
3. The crystalline form as claimed in claim 1, further characterized by an X-ray powder diffraction pattern as in Figure 1.
4. The crystalline form as claimed in claim 1, further characterized by an X-ray powder diffraction pattern as in Figure 2.
5. The crystalline form as claimed in claim 1 characterized by an infrared spectrum comprising peaks at wavenumbers of 1008 cm-1, 1317 cm-1and 2247 cm-1.
6. The crystalline form as claimed in claim 1, further characterized by an infrared spectrum as depicted in Figure 3.
7. The crystalline form as claimed in claim 1, further characterized by an infrared spectrum as depicted in Figure 4.
8. The crystalline form as claimed in claim 1, further characterized by differential scanning calorimetry (DSC) as depicted in Figure 5.
9. The crystalline form as claimed in claim 1, further characterized by differential scanning calorimetry (DSC) as depicted in Figure 6.
10. A process for preparation of the crystalline form of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole, said process comprising the following steps:
a. mixing a predetermined amount of 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole and a predetermined amount of a hydrocarbon solvent to obtain a slurry;
b. heating said slurry to a reflux temperature of said hydrocarbon solvent for a predetermined time period to obtain a heated slurry;
c. cooling said heated slurry to a first predetermined temperature to obtain a mixture;
d. filtering said mixture to obtain a solid; and
e. washing said solid with the hydrocarbon solvent and drying said solid at a second predetermined temperature to obtain 5-amino-1-(2,6-dichloro-4-trifluromethylphenyl)-3-cyano-4-ethyl sulfinyl pyrazole in crystalline form.
11. The process as claimed in claim 10, wherein the hydrocarbon solvent is at least one selected from the group consisting of methanol and ethanol.
12. The process as claimed in claim 10, wherein the predetermined time period ranges from 15 to 120 minutes.
13. The process as claimed in claim 10, wherein the first predetermined temperature ranges from 20 to 80 °C.
14. The process as claimed in claim 10, wherein the second predetermined temperature ranges from 40 to 80 °C.